Sodium Iodide → 2-[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperdin-1-yl]ethyl}phenyl)ethyl]-1H-isoindole-1,3(2H)-dione

Participants

Reaction Steps

Methanesulfonic acid 2-{4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-phenyl}-ethyl ester (Preparation 35, 20.00 g, 53.56 mmol) was dissolved in acetonitrile (80 mL) and stirred at room temperature. Sodium iodide (16.06 g, 107.12 mmol) was added portionwise and the resulting slurry heated to 80° C. for 18 h. The reaction mixture was cooled to 50° C. and further acetonitrile (80 mL) was added. To this mixture was added cyclohexyl-phenyl-(1-piperidin-4-ylmethyl-1H-[1,2,4]triazol-3-yl)-methanol (Preparation 4, 15.87 g, 53.56 mmol) and diisopropylethylamine (9.79 mL, 56.24 mmol) and heating was continued for 6 hours, then allowed to cool to room temperature. Water (160 mL) was added and the resulting slurry stirred overnight at room temperature. The solid was collected by filtration and washed with acetonitrile (5×20 mL), then dried in vacuo at 45° C. for 8 hours to yield the title compound as a brown solid in 68% yield, 20.9 g,

Provenance & Evidence